1. Field of Invention
The present invention relates generally to an apparatus and methods for producing particles that include a polymer, a wax and/or a lipid and, optionally, a biologically active substance.
2. Description of Related Art
Several processing techniques utilize the enhanced mass-transfer properties and benign nature of supercritical fluids or near-critical fluids or compressed gases (hereinafter collectively referred to as “supercritical fluids”) to produce composite or single-material particles. One of the conventional supercritical fluid processing techniques, which is sometimes referred to as the Particles from Gas-Saturated Solutions (“PGSS”) processing technique, uses a supercritical fluid to melt a solid material into a fluid or semi-fluid mass that can be sprayed into a collection vessel. The term “melt” as used in this context denotes that the supercritical fluid reduces the viscosity of the solid material (e.g., via plasticization, swelling or dissolution) so as to render it fluid or semi-fluid, which can be further processed as such. In other words, the formerly solid material can be flowed, pumped or sprayed as a fluid or semi-fluid.
The conventional PGSS particle production method exploits this characteristic by flowing the melt through a nozzle across a pressure drop into an expansion chamber that is maintained at a lower pressure than the vessel containing the melt. When the melt is sprayed through the nozzle into the expansion chamber, the supercritical fluid decompresses and rapidly expands into a gas. This causes the melt to undergo three significant changes that transform the melt into solid particles. First, as supercritical fluid expands from the melt, the remaining supercritical fluid loses its solvating power and the melt returns to a solid state. Second, the rapid expansion of the supercritical fluid into a gas results in a significant reduction in the temperature of the melt, which also assists in returning the melt to a solid phase. Third, the expansion of the supercritical fluid to a gas fractures the melt into small particles that solidify in the form of particles.
While the conventional PGSS process provides a method of forming particles at mild operating temperatures without using any potentially destructive solvents, it does suffer from several disadvantages. For example, it is very difficult to obtain particles in the low micron particle size range that have a relatively narrow particle size distribution using the conventional PGSS process. Certain biologically active materials, especially those materials that do not form a melt upon contact with supercritical fluid at mild operating conditions, simply cannot be processed using the conventional PGSS process into small particles.
Another problem with the conventional PGSS process is that it tends to form agglomerated particles, which is believed to occur as the result of the formation of bridges between particles during expansion. Moreover, the particles formed according to the conventional PGSS process tend to be irregular in shape.
Keeping the above-mentioned limitations of the conventional PGSS process in mind, it would be highly desirable to have a method for producing particles that provides the benefits of conventional PGSS processing but does not suffer from the limitations of conventional PGSS processing. Such a process would preferably produce particles having a narrow particle size distribution. Moreover, the process should also provide for enhanced control over the size and morphology of the particles produced.